On December 19, 2016, the FDA granted accelerated approval to Rubraca (rucaparib) to treat women with a certain type of ovarian cancer. Rubraca was approved for women with advanced ovarian cancer who have been treated with two or more chemotherapies and whose tumors have a specific gene mutation (deleterious BRCA), as identified by an FDA-approved companion diagnostic test.
This “approval is another example of the trend we are seeing in developing targeted agents to treat cancers caused by specific mutations in a patient’s genes,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research and acting director of the FDA’s Oncology Center of Excellence. “Women with these gene abnormalities who have tried at least two chemotherapy treatments for their ovarian cancer now have an additional treatment option.”
The National Cancer Institute estimates that 22,280 women will be diagnosed with ovarian cancer in 2016 and an estimated 14,240 will die of this disease. Approximately 15 to 20 percent of patients with ovarian cancer have a BRCA gene mutation.
BRCA genes are involved with repairing damaged DNA and normally work to prevent tumor development. However, mutations of these genes may lead to certain cancers, including ovarian cancers. Rubraca is a poly ADP-ribose polymerase (PARP) inhibitor that blocks an enzyme involved in repairing damaged DNA. By blocking this enzyme, DNA inside the cancerous cells with damaged BRCA genes may be less likely to be repaired, leading to cell death and possibly a slow-down or stoppage of tumor growth.
On December 19, 2016, the FDA also approved for use with Rubraca the FoundationFocus CDxBRCA companion diagnostic test, which is the first next-generation-sequencing (NGS)-based companion diagnostic test approved by the agency. The NGS test detects the presence of deleterious BRCA gene mutations in the tumor tissue of ovarian cancer patients. If one or more of the mutations are detected, the patient may be eligible for treatment with Rubraca.
The safety and efficacy of Rubraca were studied in two, single-arm clinical trials involving 106 participants with BRCA-mutated advanced ovarian cancer who had been treated with two or more chemotherapy regimens. Using the FoundationFocus CDxBRCA companion diagnostic, BRCA gene mutations were confirmed in 96 percent of tested trial participants with available tumor tissue. Fifty-four percent of the participants who received Rubraca in the trials experienced complete or partial shrinkage of their tumors lasting a median of 9.2 months.
Common side effects of Rubraca include nausea, fatigue, vomiting, low levels of red blood cells (anemia), abdominal pain, unusual taste sensation (dysgeusia), constipation, decreased appetite, diarrhea, low levels of blood platelets (thrombocytopenia), and trouble breathing (dyspnea). Rubraca is associated with serious risks, such as bone marrow problems (myelodysplastic syndrome), a type of cancer of the blood called acute myeloid leukemia, and fetal harm.
The FDA approved Rubraca under its accelerated approval program, which allows approval of a drug to treat a serious or life-threatening disease or condition based on clinical data showing the drug has an effect on a surrogate (substitute) endpoint that is reasonably likely to predict clinical benefit. The sponsor is continuing to study this drug in patients with advanced ovarian cancer who have BRCA gene mutations and in patients with other types of ovarian cancer. The FDA also granted the Rubraca application breakthrough therapy designation and priority review status. Rubraca also received orphan drug designation, which provides incentives such as tax credits, user fee waivers, and eligibility for exclusivity to assist and encourage the development of drugs intended to treat rare diseases.
See the FDA Announcement
See also Medical Law Perspectives, May 2015 Report: Chemotherapy: Risks and Liabilities When the Treatment Is Toxic
See also Medical Law Perspectives, October 2012 Report: Mistakes in Diagnosing Cancer: Liability Concerns for Misdiagnosis, Failure to Diagnose, and Delayed Diagnosis
See the Medical Law Perspectives June 29, 2015, Blog: Failure to Diagnose Cancer Claims Face Hurdles, Especially in New York
See the Medical Law Perspectives October 24, 2014, Blog: Medical Expert Testimony Not Necessary to Establish Standard of Care for Failure to Communicate Cancer Diagnosis